Only certain anticonvulsants protect against kainate neurotoxicity.
Kainic acid (KA), a heterocyclic structural analog of the putative excitatory neurotransmitter, glutamate (Glu), powerfully mimics many of the neuroexcitatory and neurotoxic properties of Glu. KA differs from Glu and its straight chain "excitotoxic" analogs, however, in inducing a limbic seizure-brain damage syndrome when administered subcutaneously (12 mg/kg) to adult rats. This syndrome consists of sustained seizures, resembling amygdaloid kindled seizures, and acute destruction of neural elements in limbic brain regions (amygdala, olfactory cortex, hippocampus, lateral septum and several thalamic nuclei). Early changes consist of massive edematous swelling of glia and neuronal dendrites and either swelling or dark cell changes in neuronal somata, with subsequent necrosis of many of the neurons involved. Elsewhere we demonstrated that pretreatment with morphine markedly enhances both the convulsant and brain damaging actions of KA. Here we report that pretreatment with 2 anticonvulsants (diazepam or phenobarbital) markedly reduces both athe seizure and brain damaging actions of KA, whereas, two other anticonvulsants (phenytoin or valproic acid) fail to suppress either phenomenon. Our findings suggest that a seizure mechanism underlies much of the limbic brain damage induced by systemic KA and that the toxic mechanism may have two mutually reinforcing components--a glutamergic excitatory component and a GABAergic disinhibitory component.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011759:Pyrrolidines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D011759:Pyrrolidines; D014635:Valproic Acid; D010672:Phenytoin; D003975:Diazepam; D007608:Kainic Acid; D010634:Phenobarbital